Total Asymmetric Synthesis of Glycomimetics and Polypropionates of Biological Interest

Abstract

Using readily available chiral auxiliaries such as (+)- and (?)-camphanic acid, (R,R)- and (S,S)-tartaric acid derivatives (e.g. RADO(R)-COCl, SADO(R)-COCl) efficient diastereoselective syntheses of rare sugars and glycomimetics have been developed. They engage the 'naked sugar' (enantiomerically pure 7-oxanorbornene) methodologies in which the chiral auxiliaries are recovered at an early stage of the multistep syntheses. A new reaction cascade starting with the hetero-Diels-Alder addition of sulfur dioxide to 1-(1-phenylethoxy)-1,3-dienes derived from inexpensive (+)- and (?)-1-phenylethanol allows the one-pot, four-component synthesis of polyfunctional sulfones, sulfonamides and sulfonic esters containing up to three stereogenic centers. The method ensures a high molecular and stereochemical diversity. The reaction cascade can also produce polyketide and polypropionate fragments in one-pot operations. The latter contain up to three contiguous stereogenic centers and do not have to be modified (deprotection, activation) before using them as nucleophilic partners in diastereoselective cross-aldol reactions, thus permitting the quick access to complicated polypropionate antibiotics such as Baconipyrones, Ryfamicyn S and Apoptolidines.